CN102951978A - Method for reducing acid into alcohol by sodium borohydride - Google Patents
Method for reducing acid into alcohol by sodium borohydride Download PDFInfo
- Publication number
- CN102951978A CN102951978A CN2012103695821A CN201210369582A CN102951978A CN 102951978 A CN102951978 A CN 102951978A CN 2012103695821 A CN2012103695821 A CN 2012103695821A CN 201210369582 A CN201210369582 A CN 201210369582A CN 102951978 A CN102951978 A CN 102951978A
- Authority
- CN
- China
- Prior art keywords
- sodium borohydride
- acid
- reaction
- alcohol
- solvent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000012279 sodium borohydride Substances 0.000 title claims abstract description 25
- 229910000033 sodium borohydride Inorganic materials 0.000 title claims abstract description 25
- 239000002253 acid Substances 0.000 title claims abstract description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 title claims abstract description 9
- 238000000034 method Methods 0.000 title claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 11
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 claims abstract description 10
- 230000002829 reductive effect Effects 0.000 claims abstract description 9
- 239000003444 phase transfer catalyst Substances 0.000 claims abstract description 8
- 239000002904 solvent Substances 0.000 claims abstract description 6
- -1 heterocyclic carboxylic acid Chemical class 0.000 claims description 11
- 238000003810 ethyl acetate extraction Methods 0.000 claims description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 3
- 150000002632 lipids Chemical class 0.000 claims description 3
- 239000012280 lithium aluminium hydride Substances 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 3
- 239000007810 chemical reaction solvent Substances 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- 239000003960 organic solvent Substances 0.000 abstract description 2
- 125000003118 aryl group Chemical group 0.000 abstract 1
- 239000003638 chemical reducing agent Substances 0.000 abstract 1
- 235000014113 dietary fatty acids Nutrition 0.000 abstract 1
- 229930195729 fatty acid Natural products 0.000 abstract 1
- 239000000194 fatty acid Substances 0.000 abstract 1
- 150000004665 fatty acids Chemical class 0.000 abstract 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract 1
- 238000006722 reduction reaction Methods 0.000 description 10
- 238000003756 stirring Methods 0.000 description 8
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 238000010025 steaming Methods 0.000 description 4
- KMTDMTZBNYGUNX-UHFFFAOYSA-N 4-methylbenzyl alcohol Chemical compound CC1=CC=C(CO)C=C1 KMTDMTZBNYGUNX-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- HMVYYTRDXNKRBQ-UHFFFAOYSA-N 1,3-thiazole-4-carboxylic acid Chemical compound OC(=O)C1=CSC=N1 HMVYYTRDXNKRBQ-UHFFFAOYSA-N 0.000 description 1
- CRTGSPPMTACQBL-UHFFFAOYSA-N 2,3-dihydroxycyclopent-2-en-1-one Chemical compound OC1=C(O)C(=O)CC1 CRTGSPPMTACQBL-UHFFFAOYSA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- WVDDGKGOMKODPV-UHFFFAOYSA-N OCc1ccccc1 Chemical compound OCc1ccccc1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 1
- 230000010757 Reduction Activity Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- KGYGBOORGRYDGQ-UHFFFAOYSA-N benzene;methanol Chemical compound OC.C1=CC=CC=C1 KGYGBOORGRYDGQ-UHFFFAOYSA-N 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- VSSAZBXXNIABDN-UHFFFAOYSA-N cyclohexylmethanol Chemical compound OCC1CCCCC1 VSSAZBXXNIABDN-UHFFFAOYSA-N 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000011017 operating method Methods 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for reducing acid into alcohol by sodium borohydride. The reaction is carried out as follows: changing a reaction solvent and adding a phase transfer catalyst to reduce the acid into the alcohol by the sodium borohydride under the constant temperature by using sodium borohydride as a reducing agent, water as a solvent and cetyl trimethyl ammonium bromide as the phase transfer catalyst. By using the water as the solvent, the using of organic solvent is avoided, the pollution is reduced, and the environment protection is realized; and meanwhile, lithium aluminium hydride is replaced by the sodium borohydride, the process is simplified, and the large-scale industrial production is easily performed. The system has a good effect on fatty acid, and also has a good reduction effect on some aromatic and heterocyclic acids.
Description
Technical field
The present invention relates to a kind of reduction reaction, specifically relate to the method that a kind of sodium borohydride is reduced into acid alcohol.
Background technology
The carboxylic acid reduction is one of important reaction of organic synthesis.In organic compound, carboxylic acid is the material of the difficult reduction of a class, and lithium aluminum hydride can reduce carboxylic acid and become alcohol, and this reduction reaction productive rate is higher, is the modal method of reduction carboxylic acid.But lithium aluminum hydride is relatively poor as the reductive agent selectivity, and carboxyl and other functional group all are reduced often; On the other hand, lithium aluminum hydride is expensive, and is very strict to the Non-aqueous processing requirement of reagent, and its practical application is restricted, and is difficult for suitability for industrialized production.
The sodium borohydride reduction activity is lower, generally can not reductinic acid.Reported that in recent years some sodium borohydride compound systems can well reduce carboxylic acid.Common are sodium borohydride/iodine, sodium borohydride/pyrocatechol, sodium borohydride/sulfuric acid, the sodium borohydride/systems such as Lewis acid.
Summary of the invention
The objective of the invention is in order to solve by acid reduction preparation alcohol compound, used lithium aluminum hydride is expensive and strict to the reaction system moisture requirement.By changing reaction solvent and adding phase-transfer catalyst, so that sodium borohydride can be reduced into alcohol with acid at normal temperatures.
Realize that above-mentioned purpose technical scheme of the present invention is, a kind of sodium borohydride reduction reaction of improvement, described reaction is take water as solvent, and cetyl trimethylammonium bromide is phase-transfer catalyst.
This reaction can be used for lipid acid, fragrance and heterocyclic carboxylic acid.
This reaction may further comprise the steps:
(1) take water as solvent, cetyl trimethylammonium bromide is phase-transfer catalyst, and acid compounds and sodium borohydride react at normal temperatures to reacting completely;
(2) with the reaction solution ethyl acetate extraction of step (1), distill out desolventizing, obtain corresponding alcohol compound.
Wherein, whether fully reaction is to determine by gas phase or high performance liquid chromatography.
The present invention compared with prior art has following beneficial effect: (1) reduction reaction of the present invention is as reductive agent take sodium borohydride, replaced traditional lithium aluminum hydride, reduce the danger of operating procedure, effectively controlled cost, be easier to large-scale industrial production; (2) use water to replace organic solvent, realized environmental protection; (3) the present invention is used for cetyl trimethylammonium bromide the reduction of sodium borohydride system first as phase-transfer catalyst, not only lipid acid is had good reduction effect, simultaneously test finds that also this reaction can reduce fragrance and heterocyclic carboxylic acid compound well.
Embodiment
For ease of the understanding of technical solution of the present invention, be introduced below in conjunction with concrete embodiment.
Embodiment 1:
In the 1L there-necked flask, add 128g heptanaphthenic acid, 500mL water, 10g cetyl trimethylammonium bromide, stirring at normal temperature 30min.Add the 19g sodium borohydride, water-bath cooling control temperature is not higher than 35 degree in batches.Complete rear continuation stirring at normal temperature reaction 2h.With this reaction solution 100mL*3 ethyl acetate extraction, merge organic phase, anhydrous magnesium sulfate drying revolves the steaming desolventizing, and the residuum underpressure distillation gets product cyclohexanemethanol 86g, productive rate: 76%.MS?m/z114(M+H)
+?
1H?NMR(400MHz，CDCl
3)δ：3.39(d，2H)，2.99(s，1H)，1.67-1.78(m，3H)，1.17-1.46(m，7H)，0.92(m，1H).
Embodiment 2:
In the 1L there-necked flask, add 122g phenylformic acid, 450mL water, 15g cetyl trimethylammonium bromide, stirring at normal temperature 30min.Add the 19g sodium borohydride, water-bath cooling control temperature is not higher than 35 degree in batches.Complete rear continuation stirring at normal temperature reaction 3h.With this reaction solution 100mL*3 ethyl acetate extraction, merge organic phase, anhydrous magnesium sulfate drying revolves the steaming desolventizing, and the residuum underpressure distillation gets products benzene methyl alcohol 95g, productive rate: 88%.MS?m/z108(M+H)
+?
1H?NMR(400MHz，CDCl
3)δ：7.23-7.29(m，5H)，4.52(s，2H)，3.36(s，1H).
Embodiment 3:
In the 1L there-necked flask, add 136g phenylformic acid, 600mL water, 15g cetyl trimethylammonium bromide, stirring at normal temperature 1h.Add the 19g sodium borohydride, water-bath cooling control temperature is not higher than 35 degree in batches.Complete rear continuation stirring at normal temperature reaction 3h.With this reaction solution 150mL*3 ethyl acetate extraction, merge organic phase, anhydrous magnesium sulfate drying revolves the steaming desolventizing, and the residuum underpressure distillation gets product 4-methylbenzyl alcohol 100g, productive rate: 82%.MS?m/z122(M+H)
+?
1H?NMR(400MHz，CDCl
3)δ：7.05-7.29(m，4H)，4.58(s，2H)，2.45(s，3H)，2.23(s，1H).
Embodiment 4:
In the 1L there-necked flask, add 129g 4-thiazolecarboxylic acid, 500mL water, 15g cetyl trimethylammonium bromide, stirring at normal temperature 30min.Add the 19g sodium borohydride, water-bath cooling control temperature is not higher than 35 degree in batches.Complete rear continuation stirring at normal temperature reaction 3h.With this reaction solution 150mL*3 ethyl acetate extraction, merge organic phase, anhydrous magnesium sulfate drying revolves the steaming desolventizing, and the residuum underpressure distillation gets product 4-methylbenzyl alcohol 78.2g, productive rate: 68%.MS?m/z115(M+H)
+?
1H?NMR(400MHz，CDCl
3)δ：8.85(s，1H)，7.16(s，1H)，4.35(s，2H)，2.28(s，1H).
Technique scheme has only embodied the optimal technical scheme of technical solution of the present invention, and some changes that those skilled in the art may make some part have wherein all embodied principle of the present invention, belong within protection scope of the present invention.
Claims (4)
1. a method of using sodium borohydride acid to be reduced into alcohol is characterized in that, described reaction is take water as solvent, and cetyl trimethylammonium bromide is phase-transfer catalyst.
2. reaction according to claim 1 is characterized in that, described reaction is used for sodium borohydride acid is reduced into alcohol.
3. reaction according to claim 1 and 2 is characterized in that, described reaction comprises the reduction of lipid acid, aromatic acid and heterocyclic carboxylic acid.
4. according to claim 1,2 or 3 described reactions, it is characterized in that, described reaction may further comprise the steps:
(1) take water as solvent, cetyl trimethylammonium bromide is phase-transfer catalyst, and acid compounds and sodium borohydride react at normal temperatures to reacting completely;
(2) with the reaction solution ethyl acetate extraction of step (1), distill out desolventizing, obtain corresponding alcohol compound.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210369582.1A CN102951978B (en) | 2012-09-28 | 2012-09-28 | Method for reducing acid into alcohol by sodium borohydride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210369582.1A CN102951978B (en) | 2012-09-28 | 2012-09-28 | Method for reducing acid into alcohol by sodium borohydride |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102951978A true CN102951978A (en) | 2013-03-06 |
| CN102951978B CN102951978B (en) | 2014-07-16 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210369582.1A Active CN102951978B (en) | 2012-09-28 | 2012-09-28 | Method for reducing acid into alcohol by sodium borohydride |
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| Country | Link |
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| CN (1) | CN102951978B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108610238A (en) * | 2018-06-12 | 2018-10-02 | 黄石法姆药业股份有限公司 | A kind of synthetic method of cyclohexanemethanol |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102531843A (en) * | 2010-12-30 | 2012-07-04 | 上海恩氟佳科技有限公司 | Method for catalytically hydrogenating difluoroacetic acid |
-
2012
- 2012-09-28 CN CN201210369582.1A patent/CN102951978B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102531843A (en) * | 2010-12-30 | 2012-07-04 | 上海恩氟佳科技有限公司 | Method for catalytically hydrogenating difluoroacetic acid |
Non-Patent Citations (1)
| Title |
|---|
| 车荣睿: "硼氢化钠在有机合成中的新应用", 《化学试剂》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108610238A (en) * | 2018-06-12 | 2018-10-02 | 黄石法姆药业股份有限公司 | A kind of synthetic method of cyclohexanemethanol |
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| Publication number | Publication date |
|---|---|
| CN102951978B (en) | 2014-07-16 |
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Application publication date: 20130306 Assignee: TIANJIN HI-TECH PRODUCTIVITY PROMOTION CO.,LTD. Assignor: TIANJIN SCIPHARMACN Ltd. Contract record no.: 2014120000094 Denomination of invention: Method for reducing acid into alcohol by sodium borohydride Granted publication date: 20140716 License type: Exclusive License Record date: 20141030 |
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| EC01 | Cancellation of recordation of patent licensing contract |
Assignee: TIANJIN HI-TECH PRODUCTIVITY PROMOTION CO.,LTD. Assignor: TIANJIN SCIPHARMACN Ltd. Contract record no.: 2014120000094 Date of cancellation: 20180228 |
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Effective date of registration: 20240206 Address after: No. 4 Xi'an Road, South District, Jinghai Economic Development Zone, Jinghai District, Tianjin City, 301699 Patentee after: TIANJIN HESHENG MEDICAL TECHNOLOGY DEVELOPMENT Co.,Ltd. Country or region after: China Address before: Room 501, Building F, Green Industry Base, No. 6 Haitai Development Road, Huayuan Industrial Park (Outer Ring), Xiqing District, Tianjin, 300381 Patentee before: TIANJIN SCIPHARMACN Ltd. Country or region before: China |